Predictive Insights Into Bioactive Compounds from Streptomyces as Inhibitors of SARS-CoV-2 Mutant Strains by Receptor Binding Domain: Molecular Docking and Dynamics Simulation Approaches

AuthorHourieh Kalhoren
AuthorMohammad Hossein Mokhtarianen
AuthorHamzeh Rahimien
AuthorBehzad Shahbazien
AuthorReyhaneh Kalhoren
AuthorTahereh Komeili Movaheden
AuthorHoda Abolhasanien
OrcidMohammad Hossein Mokhtarian [0000-0003-4511-6376]en
Issued Date2024-12-31en
AbstractBackground: The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the angiotensin-converting enzyme 2 (ACE2) receptor in humans. To date, numerous SARS-CoV-2 variants, particularly those involving mutations in the RBD, have been identified. These variants exhibit differences in transmission, pathogenicity, diagnostics, and vaccine efficacy. Objectives: Although therapeutic agents are currently available to inhibit SARS-CoV-2, most provide supportive and symptomatic relief. Moreover, different variants may exhibit resistance to these treatments. This study aimed to identify a potential compound with favorable antiviral effects against SARS-CoV-2 variants. Methods: The study explored drug discovery through structure-based virtual screening of natural products (NPs) from the StreptomeDB database, targeting the ACE2-binding pocket of the SARS-CoV-2 RBD protein. The analysis included the wild-type protein (PDB ID: 6VW1) as well as the Alpha, Beta, Delta, Lambda, Omicron/BA.1, and Omicron/BA.2 variants. Results: In silico screening identified ‘Stambomycin B’ as a potential compound with the highest binding affinity. Molecular dynamics simulations of the complexes, conducted over 100 ns, confirmed the prediction that ‘Stambomycin B’ could inhibit different SARS-CoV-2 variants effectively. Conclusions: This study concludes that ‘Stambomycin B’, a macrolide compound produced by Streptomyces ambofaciens, may be a candidate NP for effectively combating all mutants that occur in the binding of SARS-CoV-2 RBD to ACE2, even those that may arise in the future.en
DOIhttps://doi.org/10.5812/ijpr-150879en
KeywordSARS-CoV-2en
KeywordACE2en
KeywordStambomycin Ben
KeywordMolecular Dockingen
KeywordMolecular Dynamics Simulationen
PublisherBrieflandsen
TitlePredictive Insights Into Bioactive Compounds from Streptomyces as Inhibitors of SARS-CoV-2 Mutant Strains by Receptor Binding Domain: Molecular Docking and Dynamics Simulation Approachesen
TypeResearch Articleen

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